Transcriptional profiling of livers from different strain of mice treated with Asparaginase

Asparaginase (ASNase) is widely used to treat acute lymphoblastic leukemia (ALL) in children but it causes metabolic complications related to liver toxicity. ASNase results in synthesis of some factors such as ATF4. The eIF2-ATF4 pathway is essential for cell survival during amino acid starvation conditions. Activation of the AAR in liver requires the eIF2 kinase called general control nonderepressible 2 kinase (GCN2). To what extent activation of the GCN2-eIF2-AAR is mediated by ATF4 is unknown. Our objective and hypothesis are addressed in our aim to describe the liver response to ASNase in mice deleted for Atf4. RNA sequencing alongside complementary biochemical approaches were performed in the livers of mice treated with eight daily injections of ASNase or saline excipient. Differences in gene expression were evaluated. We also explored the relationship between the different treatment groups and strains. This research provides insight into the importance of genetic background of patients in choosing ASNase as a treatment.